A long-term goal of neuroscience is to understand how the brain processes sensory input to perceive the world. While much has been learned about the mechanisms of sensory stimulus transduction, how neurons and circuits in the brain's cerebral cortex process that sensory information is much less clear. A basic unanswered question is: are neurons the fundamental unit for sensory processing, or do smaller structures such as dendrites serve this role? Traditionally, models of cortical processing assume synaptic inputs are randomly distributed onto dendrites and linearly integrated at the soma. Recent experiments have demonstrated that dendrites can behave as semi-independent compartments that integrate inputs nonlinearly. These data, combined with Hebbian plasticity rules, predict that functionally related inputs should be clustered onto separate dendritic compartments ("dendritic domains"). However, whether the classical, "soma-based integration model", or the "dendritic domain-based integration model" applies during sensory processing in cerebral cortex is not known. In particular, whether non-linear dendritic integration is a general rule of cortical processing, and whether clusters of functionally related inputs are present at the dendritic level in vivo, is not known. Here I propose experiments to determine whether non-linear integration and clustered inputs are utilized within intact primary sensory cortex. I will perform these experiments in rodent somatosensory cortex, a powerful model system for studying sensory processing. I will first use in vitro 2-photon imaging and electrophysiology to determine if the proximal basal dendrites of layer 2/3 pyramidal neurons, which are the primary recipients of feedforward sensory inputs from layer 4, act as nonlinear integration compartments. I will then monitor the dendritic calcium levels of layer 2/3 dendrites in vivo using 2-photon imaging to determine if functionally related inputs from the intact whisker pathway are clustered onto the same dendritic compartment. This proposal will give me valuable training in 2-photon imaging and electrophysiology within sensory cortex, both in vitro and in vivo. The results of these experiments will clarify the pattern of synaptic integration in sensory cortex, and will inform our theoretical understanding of how the brain processes sensory inputs. The results may be relevant to understanding autism, epilepsy, and other neurological disorders in which cortical sensory processing and excitability are compromised. PUBLIC HEALTH RELEVANCE: The proposed research will study how neurons in the brain process sensory information. By measuring neural responses to tactile sensory stimulation using optical and physiological recording techniques in a rodent model, we will learn how inputs are integrated within dendrites of neurons. The knowledge gained will improve our understanding of sensory processing in normal brains, which may give insight into neurological diseases such as autism or epilepsy in which sensory processing is compromised.